Search PubMed⌕ Search

Biomedical subjects

B D Goldstein

Publications and source records attributed to B D Goldstein.

At least 181 records · Page 10Linked to original sources
PubMed1970

Ozone and vitamin E.

Vitamin E deficiency in rats is associated with a greater susceptibility to lethal levels of ozone. Exposure of rats to sublethal ozone concentrations produces an accelerated decline in serum vitamin E levels. These findings are consistent with the possibility that lipid peroxidation is a mechanism of ozone toxicity.

Aging↗
PubMedDate not supplied

The pulmonary and extrapulmonary effects of ozone.

The toxicity of ozone is solely due to its action as an oxidant. It is an extremely reactive gas which rapidly forms intermediate oxidizing derivatives after inhalation. High concentrations cause death from pulmonary oedema. Both pulmonary and extrapulmonary toxicity have been observed at lower concentrations of ozone, including those currently present in urban air. Pulmonary cellular and subcellular membranes appear to be particularly susceptible. A primary mechanism of this effect is the oxidative decomposition of polyunsaturated fatty acids, which has been demonstrated in rodent lungs after inhalation of ozone. Supporting evidence includes the potentiation of ozone toxicity by vitamin E deficiency and an increased use of this antioxidant vitamin during repetitive exposure to ozone. Other membrane effects include oxidation of thiol groups and, perhaps, of tryptophan. Microsomal alterations include a loss of lung cytochrome P450 which may also be related to lipid peroxidation. Extrapulmonary toxicity is not directly due to ozone but may represent in effect due to lipid peroxide decomposition products, particularly malonaldehyde. This three-carbon dialdehyde has been shown to alter cell membrane fluidity and to have mutagenic properties; the latter perhaps due to cross-linkage of DNA to histone.

Amino Acids↗
PubMedDate not supplied

Inhibition by reactive aldehydes of superoxide anion radical production in stimulated human neutrophils.

alpha,beta-Unsaturated aldehydes were investigated in vitro for their ability to inhibit superoxide anion radical (O2-.) production in stimulated human polymorphonuclear leukocytes (PMN). The aldehydes investigated were (i) trans-4-hydroxynonenal and malonaldehyde (MDA), two toxic lipid peroxidation products; (ii) acrolein and crotonaldehyde, two air pollutants derived from fossil fuel combustion; (iii) trans,trans-muconaldehyde, a putative hematotoxic benzene metabolite. Preincubation of PMN with reactive aldehydes followed by stimulation with the oxygen burst initiator phorbol myristate acetate (PMA) resulted in a dose-dependent inhibition of O2-. production. The concentration at which 50% inhibition (IC50) was observed was 21 microM for acrolein, 23 microM for trans,trans-muconaldehyde, 27 microM for trans-4-hydroxynonenal and 330 microM for crotonaldehyde. A similar inhibitory effect by these aldehydes was observed in digitonin- and concanavalin A-stimulated PMN. MDA inhibited O2-. production in PMA-stimulated PMN by 100% at 10(-2) M but gave no inhibition at 10(-3) M. The standard aldehyde propionaldehyde did not inhibit O2-. production at 10(-3)-10(-6) M. Preincubation of PMN with acrolein in the presence of cysteine completely protected against the inhibitory effect of this reactive aldehyde. The results indicate that the ability of toxic aldehydes to inhibit O2-. production in stimulated PMN correlates directly with their alkylation potential which is a function of the electrophilicity of the beta carbon.

Acrolein↗
PubMedDate not supplied

Reaction of (E,E)-muconaldehyde and its aldehydic metabolites, (E,E)-6-oxohexadienoic acid and (E,E)-6-hydroxyhexa-2,4-dienal, with glutathione.

(E,E)-Muconaldehyde (muconaldehyde) has been identified as a hematotoxic metabolite of benzene in vitro. It is metabolized in mouse liver cytosol to oxidized and reduced derivatives including the alpha, beta-unsaturated aldehydes (E,E)-6-oxohexadienoic acid and (E,E)-6-hydroxy-2,4-hexadienal. In this study we have synthesized the aldehydic metabolites of muconaldehyde. The reaction of glutathione with muconaldehyde and its aldehyde metabolites was investigated. Reactions were bimolecular and stoichiometric in aldehyde and glutathione in the initial phases. Second-order rate constants were determined, and the rates were in the order muconaldehyde > (E,E)-6-hydroxy-2,4-hexadienal > (E,E)-6-oxohexadienoic acid. Further investigation of the reaction of muconaldehyde with glutathione showed that the bimolecular reaction is reversible but the initial product decomposed irreversibly to two or more products, one of which had a red-shifted UV spectrum. Rate constants for these subsequent reactions were determined. The results are discussed in terms of the toxicity of muconaldehyde at tissues distal from the liver, where it is believed to be formed from the metabolism of benzene.

Aldehydes↗
PubMedDate not supplied

Risk assessment methodology: maximum tolerated dose and two-stage carcinogenesis models.

The Committee on Risk Assessment Methodology of the Board on Environmental Studies and Toxicology of the National Academy of Sciences has considered issues related to the use of the maximum tolerated dose (MTD) in carcinogenesis bioassays and of 2-stage models of carcinogenesis. In each case, the goal has been to consider whether sufficient information is available to lead to a change in current methodology used by regulatory agencies in assessing risk. The majority of the committee favored retention of the MTD but recommended that lower doses also be used for cancer bioassays and, if the results are positive, performance of additional mechanistic studies aimed at improved extrapolation to environmentally relevant concentrations. The minority recommended that additional preliminary studies be done in order to obtain information about the highest dose relevant to extrapolation to humans for use in the cancer bioassay. Two-stage carcinogenesis models were found to be an excellent approach to increase understanding but required an extensive toxicological data base beyond that available for most chemicals. These deliberations have highlighted the value of increased understanding of the basic mechanisms of action of potential cancer-causing chemicals in order to advance the methodology of risk assessment.

Animals↗
PubMedDate not supplied

Salud Ocupacional.

Explore the source record for details and available documents.

Academies and Institutes↗
PubMedDate not supplied

Capsaicin's effect on rat nasal mucosa substance P release: experimental basis for vasomotor rhinitis treatment.

Substance P (SP) is one of several neuropeptides found in nasal mucosa. It exists primarily in sensory afferent neurons, which are best demonstrated by immunohistochemical staining. These substance P-like immunoreactive (SPLI) nerve fibers are unmyelinated C fibers, which connect to the trigeminal ganglion and the spinal trigeminal nucleus. They are found around vessels and seromucinous glands in the submucosa. When the nasal mucosa receives a noxious stimulus, SP is released and acts orthodromically as a comediator of nasal pain, while antidromically it induces vasodilatation, plasma extravasation, mucosal edema, and rhinorrhea. Its antidromic effects have been implicated in vasomotor rhinitis and can be blocked by topical intranasal capsaicin application. Wolf and others have demonstrated in human subjects that vasomotor rhinitis can be blocked up to 1 year by a series of intranasal capsaicin applications. It has not yet been demonstrated that nasal mucous SP levels following noxious nasal stimulus change after intranasal capsaicin pretreatment. Consequently a project was designed to determine whether intranasal capsaicin pretreatment would affect nasal substance P release measured in nasal secretion. Nasal secretion SP levels were measured before and after noxious nasal stimulus in controls and in capsaicin pretreated rats. The difference in measured nasal secretion SP levels were significant (p < 0.05).

Administration, Intranasal↗
PubMedDate not supplied

Biological markers and risk assessment.

Biological markers provide the opportunity to rapidly advance the field of risk assessment for both workers and the general population. Markers of exposure allow much more accurate assessment of exposure than currently possible using mathematical models of dispersion and uptake. Markers of effect can lead to the prediction of disease sufficiently early to avoid adverse outcomes in workers or the general population. Linkage of predictors of effect with markers of exposure can provide dose-response information of unique relevance to the problems of extrapolating from high to low dose and from animals to humans. Biological markers of susceptibility allow definition of the populations for whom risk characterization is particularly of importance. Development of biological markers suitable for risk assessment requires careful validation and faces impediments due to the overreliance of regulators on mathematical models, which inhibits the development of new bioscience, and due to misplaced concerns about ethical experimental exposures of humans to environmental levels of pollutants. The path to developing biological markers of exposure, effect, or susceptibility of value in risk assessment is primarily through improving basic biomedical understanding.

Biomarkers↗
PubMedDate not supplied

Benzene toxicity.

The proper control of benzene in the workplace and the general environment has been a subject of relatively intense interest for at least the past decade. The author reviews the toxicology of benzene, its hematologic effects in the human, and methods of measurement of benzene exposure in the workplace.

Anemia, Aplastic↗